Cardiovascular Diseases That Have Emerged From the Darkness

It is important for both the patient and physician communities to have timely access to information recognizing rapid progress in the diagnosis and treatment of familiar but relatively uncommon cardiovascular diseases. Patients with 3 cardiovascular diseases (ie, hypertrophic cardiomyopathy, pulmonary arterial hypertension, and transthyretin (TTR) cardiac amyloidosis (ATTR)]), once considered rare without effective management options and associated with malignant prognosis, have now benefited substantially from the development of a variety of innovative therapeutic strategies. In addition, in each case, enhanced diagnostic testing has expanded the patient population and allowed for more widespread administration of contemporary treatments. In hypertrophic cardiomyopathy, introduction of implantable defibrillators to prevent sudden death as well as high-benefit:low-risk septal reduction therapies to reverse heart failure have substantially reduced morbidity and disease-related mortality (to 0.5% per year). For pulmonary arterial hypertension, a disease once characterized by a particularly grim prognosis, prospective randomized drug trials with aggressive single (or combined) pharmacotherapy have measurably improved survival and quality of life for many patients. In cardiac amyloidosis, development of disease-specific drugs can for the first time reduce morbidity and mortality, prominently with breakthrough ATTR-protein-stabilizing tafamidis. In conclusion, in less common and visible cardiovascular diseases, it is crucial to recognize substantial progress and achievement, given that penetration of such information into clinical practice and the patient community can be inconsistent. Diseases such as hypertrophic cardiomyopathy, pulmonary arterial hypertension, and ATTR cardiac amyloidosis, once linked to a uniformly adverse prognosis, are now associated with the opportunity for patients to experience satisfactory quality of life and extended longevity

Cardiac amyloidosis: the great pretender

Cardiac amyloidosis (CA) is often misdiagnosed because of both physician-related and disease-related reasons including: fragmented knowledge among different specialties and subspecialties, shortage of centres and specialists dedicated to disease management, erroneous belief it is an incurable disease, rarity of the condition, intrinsic phenotypic heterogeneity, genotypic heterogeneity in transthyretin-related forms and the necessity of target organ tissue histological diagnosis in the vast majority of cases. Pitfalls, incorrect beliefs and deceits challenge not only the path to the diagnosis of CA but also the precise identification of aetiological subtype. The awareness of this condition is the most important prerequisite for the management of the risk of underdiagnoses and misdiagnosis. Almost all clinical, imaging and laboratory tests can be misinterpreted, but fortunately each of these diagnostic steps can also offer diagnostic “red flags” (i.e. highly suggestive findings that can foster the correct diagnostic suspicion and facilitate early, timely diagnosis). This is especially important because outcomes in CA are largely driven by the severity of cardiac dysfunction and emerging therapies are aimed at preventing further amyloid deposition

Proposed Cardiac End Points for Clinical Trials in Immunoglobulin Light Chain Amyloidosis: Report From the Amyloidosis Forum Cardiac Working Group

Immunoglobulin light chain amyloidosis is a rare, multisystemic, phenotypically heterogenous disease affecting cardiovascular, renal, neurological, and gastrointestinal systems to varying degrees. Its underlying cause is a plasma cell dyscrasia characterized by misfolding of monoclonal immunoglobulin light chains which leads to aggregation and deposition of insoluble amyloid fibrils in target organs. Prognosis is primarily dependent on extent of cardiac involvement and depth of hematologic response to treatment. To facilitate development of new therapies, a public-private partnership was formed between the nonprofit Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research. In 2020, the Amyloidosis Forum launched an initiative to identify novel/composite end points and analytic strategies to expedite clinical trials for development of new therapies for the primary hematologic disorder and organ system manifestations. Specialized working groups identified organ-specific end points; additional working groups reviewed health-related quality of life measures and statistical approaches to data analysis. Each working group comprised amyloidosis experts, patient representatives, statisticians, and representatives from the Food and Drug Administration, the UK Medicines and Healthcare Products Regulatory Agency, and pharmaceutical companies. This review summarizes the proceedings and recommendations of the Cardiac Working Group. Using a modified Delphi method, the group identified, reviewed, and prioritized cardiac end points relevant to immunoglobulin light chain amyloidosis in the context of an antiplasma cell therapy. Prioritized cardiovascular end points included overall survival, hospitalization, N-terminal pro-B-type natriuretic peptide level, 6-minute walk test, Kansas City Cardiac Questionnaire, and cardiac deterioration progression-free survival. These recommended components will be further explored through evaluation of clinical trial datasets and formal guidance from regulatory authorities

Perspectives on Implementing a Multidomain Approach to Caring for Older Adults With Heart Failure

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153220/1/jgs16183_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153220/2/jgs16183-sup-0001-supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153220/3/jgs16183.pd

Transthyretin cardiac amyloidosis in continental Western Europe: an insight through the Transthyretin Amyloidosis Outcomes Survey (THAOS)

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Feasibility of a mHealth Approach to Nutrition Counseling in an Appalachian State

Abstract: West Virginia is a rural state with an aging population that may experience barriers to accessing nutritional and lifestyle counseling. This study examined feasibility of an online personalized nutrition tracking application, Good Measures (GM), with patients at seven health care clinics throughout the state. Fourteen healthcare providers and 64 patients 18 years or older with a Body Mass Index (BMI) greater than or equal to 30 and access to the Internet were recruited for this 12-week feasibility study. Patient participants logged meals and exercise into the GM application via smart phone, tablet, or computer and virtually engaged with a Registered Dietitian Nutritionist (RDN) in one-on-one sessions. The primary endpoint was to examine feasibility of the program by usage of the application and feedback questions regarding the benefits and challenges of the application. Participants were predominately white (92%) and female (76%). Minimal improvements in weight and systolic blood pressure were found. Participant attitude survey data declined from 4-weeks to 12-weeks of the intervention. Interestingly though, patients in a rural clinic had lesser declines in attitudes than peri-urban participants. Qualitative feedback data identified participants predominately had a positive overall feeling toward the approach. Participants expressed favorability of RDN access, the variety of foods, but did give suggestions for in-person meetings and more updating of the application. Implementing a technology approach to nutrition in rural areas of West Virginia using a mobile application with RDN access may be one strategy to address public health issues such as obesity

Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS):14-year update

Abstract Background Transthyretin amyloidosis (ATTR amyloidosis) is a rare, life-threatening disease caused by the accumulation of variant or wild-type (ATTRwt amyloidosis) transthyretin amyloid fibrils in the heart, peripheral nerves, and other tissues and organs. Methods Established in 2007, the Transthyretin Amyloidosis Outcomes Survey (THAOS) is the largest ongoing, global, longitudinal observational study of patients with ATTR amyloidosis, including both inherited and wild-type disease, and asymptomatic carriers of pathogenic TTR mutations. This descriptive analysis examines baseline characteristics of symptomatic patients and asymptomatic gene carriers enrolled in THAOS since its inception in 2007 (data cutoff: August 1, 2021). Results This analysis included 3779 symptomatic patients and 1830 asymptomatic gene carriers. Symptomatic patients were predominantly male (71.4%) and had a mean (standard deviation [SD]) age of symptom onset of 56.3 (17.8) years. Val30Met was the most common genotype in symptomatic patients in South America (80.9%), Europe (55.4%), and Asia (50.5%), and more patients had early- versus late-onset disease in these regions. The majority of symptomatic patients in North America (58.8%) had ATTRwt amyloidosis. The overall distribution of phenotypes in symptomatic patients was predominantly cardiac (40.7%), predominantly neurologic (40.1%), mixed (16.6%), and no phenotype (2.5%). In asymptomatic gene carriers, mean (SD) age at enrollment was 42.4 (15.7) years, 42.4% were male, and 73.2% carried the Val30Met mutation. Conclusions This 14-year global overview of THAOS in over 5000 patients represents the largest analysis of ATTR amyloidosis to date and highlights the genotypic and phenotypic heterogeneity of the disease. ClinicalTrials.gov Identifier: NCT00628745.http://deepblue.lib.umich.edu/bitstream/2027.42/173793/1/13023_2022_Article_2359.pd

Effects of Mavacamten on Measures of Cardiopulmonary Exercise Testing Beyond Peak Oxygen Consumption: A Secondary Analysis of the EXPLORER-HCM Randomized Trial

IMPORTANCE: Mavacamten, a cardiac myosin inhibitor, improved peak oxygen uptake (pVO2) in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in the EXPLORER-HCM study. However, the full extent of mavacamten's effects on exercise performance remains unclear. OBJECTIVE: To investigate the effect of mavacamten on exercise physiology using cardiopulmonary exercise testing (CPET). DESIGN, SETTING, AND PARTICIPANTS: Exploratory analyses of the data from the EXPLORER-HCM study, a randomized, double-blind, placebo-controlled, phase 3 trial that was conducted in 68 cardiovascular centers in 13 countries. In total, 251 patients with symptomatic obstructive HCM were enrolled. INTERVENTIONS: Patients were randomly assigned in a 1:1 ratio to mavacamten or placebo. MAIN OUTCOMES AND MEASURES: The following prespecified exploratory cardiovascular and performance parameters were assessed with a standardized treadmill or bicycle ergometer test protocol at baseline and week 30: carbon dioxide output (VCO2), minute ventilation (VE), peak VE/VCO2 ratio, ventilatory efficiency (VE/VCO2 slope), peak respiratory exchange ratio (RER), peak circulatory power, ventilatory power, ventilatory threshold, peak metabolic equivalents (METs), peak exercise time, partial pressure of end-tidal carbon dioxide (PETCO2), and VO2/workload slope. RESULTS: Two hundred fifty-one patients were enrolled. The mean (SD) age was 58.5 (11.9) years and 59% of patients were male. There were significant improvements with mavacamten vs placebo in the following peak-exercise CPET parameters: peak VE/VCO2 ratio (least squares [LS] mean difference, -2.2; 95% CI, -3.05 to -1.26; P < .001), peak METs (LS mean difference, 0.4; 95% CI, 0.17-0.60; P < .001), peak circulatory power (LS mean difference, 372.9 mL/kg/min × mm Hg; 95% CI, 153.12-592.61; P = .001), and peak PETCO2 (LS mean difference, 2.0 mm Hg; 95% CI, 1.12-2.79; P < .001). Mavacamten also improved peak exercise time compared with placebo (LS mean difference, 0.7 minutes; 95% CI, 0.13-1.24; P = .02). There was a significant improvement in nonpeak-exercise CPET parameters, such as VE/VCO2 slope (LS mean difference, -2.6; 95% CI, -3.58 to -1.52; P < .001) and ventilatory power (LS mean difference, 0.6 mm Hg; 95% CI, 0.29-0.90; P < .001) favoring mavacamten vs placebo. CONCLUSIONS AND RELEVANCE: Mavacamten improved a range of CPET parameters beyond pVO2, indicating consistent and broad benefits on maximal exercise capacity. Although improvements in peak-exercise CPET parameters are clinically meaningful, the favorable effects of mavacamten on submaximal exertional tolerance provide further insights into the beneficial impact of mavacamten in patients with obstructive HCM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03470545